Current status: Biochemical reactions in living systems take place in an environment crowded by various macromolecules and ligands. Therefore, experimental data obtained in buffers do not reflect in vivo conditions. We will use various crowding agents such as glycerol, poly(ethylene glycol) (PEG) etc. in water solutions to investigate the influence of the crowded environment on various biochemical reactions such as transcription, translation, or cleavage of plasmid DNA by restriction enzyme. We have already observed that in some crowding environments, cleavage of DNA can be stopped at some moderate concentration of PEG solution. Such studies are also important for a design of artificial cells. Inspiration for this PhD topic comes from the papers of W. Huck group: Nature Nanotechnology, 9, 406-407(2014); PNAS 110, 11692-11697(2013) and R. Holyst group Soft Matter, 7,3092-3099(2011); Nucleic Acids Research, 42, 727-738(2014); Soft Matter, 9, 4386-4389 (2013).

The goal: To determine an influence of various physical factors i.e. viscosity, depletion and osmotic pressure, at the nanoscale on the rate of biochemical reactions in crowded environment.

Our approach: We will use Fluorescence Correlation Spectroscopy(FCS), Raster Image Correlation Spectroscopy (RICS) and typical biochemical assays. We will concentrate on typical reactions occurring in living cells such as transcription and translation, but we will also consider motion of molecular motors on microtubules and DNA cleavage by restriction enzymes. We will additionally model FCS curves in order to extract both the equilibrium constants for reactions and the reaction rates. We would like to quantify various factors influencing biochemical reactions in crowded environment.

Current status: Small molecules, proteins, and DNA fragments move relatively easily through gels. This observation is commonly used in gel electrophoresis, a method for separation and analysis of macromolecules DNA, RNA, proteins and their fragments, based on their size and charge. Their mobility is affected by the viscosity of the solvent, their size, charge and degree of cross-linking of the gel. At the macroscale gel is purely elastic, while at the nanoscale it is a viscous medium. We formulate the following questions: how does a viscous flow cross-over to a motion under the influence of the elastic force? What is the difference between Young modulus at nano- and at macroscale? At what lengthscale can we observe an influence of the nanoscale elasticity on mobility of small molecules? Part of the inspiration for these studies comes from the publication co-authored by H-J. Butt and R.Holyst (Nano Letters 11,2157-2163, (2011)).

The goal: To determine the Young modulus at macro & nanoscale and determine the crossover length scale between viscous flow in gels at the nanoscale and elastic response of the gel at the macroscale.

Our approach: We will use Fluorescence Correlation Spectroscopy (FCS), Atomic Force Microscopy, Surface Probe Microscopy to monitor mobility of proteins in gels and Young modulus of the gel. We will also apply electric field to study mobility of proteins/DNA in gels. For viscous flow at nanoscale we will use a concept of length scale dependent viscosity from our Nano Letters paper. H-J. Butt is an expert in Surface Probe Microscopy and both groups use FCS to study mobility of nano-probes in polymer systems (e.g. ACS Macro Letters, 4, 171-176 (2015); Physical Review Letters< 111, 228301, (2013)).

Current status: Information processing with different types of chemical media has been studied for a long time. It is expected that chemical information processing devices can be reduced to nano-scale & work autonomously. Therefore, chemical computers seem to fit specific applications like intelligent nano-materials, smart drugs or deep space sensors where mass, and size reduction is crucial. Typical chemical information processing devices are constructed as networks of communicating nonlinear elements. There are many factors, e.g. character of nonlinear medium, type of communication or the geometry of interactions between processing elements that should be taken into account to design a device performing a specific function. Currently, chemical information processing devices are constructed with bottom-up approach: simple elements (e.g. logic gates) are invented & more complex operations are realized by concatenation of simple operations. We plan to develop algorithms that can optimize a selected complex structure of communicating nonlinear elements in order to achieve its max. functionality with respect to a specific information processing task. Inspiration for this PhD topic comes from the publications co-authored by J. Gorecki and P. Dittrich (Phil. Trans. R. Soc. A 373 (2015) 20140219;, International Journal of Neural Systems, 25, (2015), 1450032).

The goal: To write evolutionary algorithms that optimize the functionality of a given network of communicating chemical nonlinear elements for a specific information processing task.

Our approach: The project is multidisciplinary and covers: the evolutionary algorithms, information theory, theory of nonlinear processes, chemical kinetics & computer simulations of nano-scale systems with complex chemical reactions. Bearing in mind the problem complexity, we would like to apply the evolutionary algorithms to the automatic design. The fitness function optimized within the evolution will measure the mutual information between the system evolution and the expected answer of the device.

Current status: Ordered spatial patterns can appear as the result of different surface phenomena like dewetting or evaporation. There are also experimental results showing transient oscillations during evaporation of a multicomponent fluid. These processes have been already used in technology, because they can produce large scale spatial structures if they proceed in strictly controlled non-equilibrium conditions. Precipitation patterns obtained through evaporation of solvent can be used to fabricate nano- and micro- structures with required morphology. However, the theory of such processes is at the early developments stage and it is not adequate for quantitative predictions of structures that are formed at specific conditions. Within the project we plan to develop a theoretical approach that describes structure patterns and morphology of nanoclusters that appear as the result of evaporation. Inspiration for this PhD topic comes from the papers of M. M. Hanczyc group (Langmuir, 30, (2014), 11937-11944) and J. Górecki group (J. Phys. Chem. C, 117, 13080-13086 (2013)).

The goal: To present a theory that describes structure patterns and morphology of nanoclusters that appear as the result of evaporation.

Our approach: The project will cover both theory and experiments. The experimental part will be concerned with studies on spatiotemporal structures formed by evaporation in precisely controlled conditions. Electron microscopy will be used to investigate the morphology of nanoclusters. The theory will be based on hydrodynamic equations that take into account transport in time-dependent crowded environment. We also plan to perform computer simulations of pattern formation at meso- and nanoscales.

5

Spectroscopy and photoreactivity on the level of custom-designed single molecules

Current status: The progress in optical and scanning microscopies has enabled the detection and monitoring of single molecules using different detection techniques: (1) fluorescence; (2) Raman (especially when surface- and resonance-enhanced); (3) scanning tunnelling and atomic force microscopy. For a successful experiment on a single molecule level a crucial factor is the (photo)stability of a particular chromophore. It strongly depends on many intramolecular and external factors. Inspiration for this PhD topic comes from the publication co-authored by J. Waluk and J. Meixner (J. Am. Chem. Soc. 2005, 127, 5302-5303) and J. Waluk group (J. Phys. Chem. Lett. 2013, 4, 3967−3971).

The goal: To synthesize and fully characterize molecules of which, for a given surrounding, the photoreactivity, and therefore photostability can be controlled.

Our approach: The objects for study will be selected on the basis of previously accumulated knowledge, using our expertise in spectroscopy and organic synthesis. The experiments will include stationary and time-resolved measurements of electronic and vibrational spectra in combination with various microscopic methods; the support from quantum-chemical calculations will also be provided. The results may find applications in the design of fluorescence/Raman molecular probes, new dyes and photosensitizers.

6

Effect of fluctuations in biological processes confined in nanoscale organs

Bogdan Nowakowski

Annie LemarchandUniversity Pierre and Marie Curie, France

Current status: The influence of fluctuations in biological systems has become a subject of intensive investigations since the rapid development of bioengineering and biochemical processing. Internal fluctuations may be an especially important issue in biological processes which are often restricted to nanoscale domains, where intrinsic stochastic perturbations reach a relatively higher level. Moreover, biochemical reactions are governed - as a rule - by nonlinear dynamics, which is particularly sensitive to even small perturbations of the average, deterministic evolution. In development processes, like genetic reproduction or cell differentiation, minor errors at the nanoscale are known to lead to significant phenotypical misexpressions. Inspiration for this PhD topic comes from the publication co-authored by B. Nowakowski and A. Lemarchand in J Chem Phys., 137, 074107 (2012)) and from the publication of B. Nowakowski group (J Chem Phys., 141, 124106 (2014)).

The goal: The present study should analyse in detail the robustness of dynamics to random perturbations, with focus on possible occurrence of morphogenesis mutations and metabolism malfunctions.

Our approach: The study will include (i) a theoretical approach with approximate (possibly analytical) calculations, (ii) simulations at different description levels: from deterministic scale to particle scale through stochastic, mesoscopic scale. Selection of the systems should be done in collaboration with a bioengineering company.

7

Mechanism of nanostructure formation and surface engineering for activated materials in catalysis

Current status: The growing concerns related to petroleum-based fuels, together with environmental & health regulations, indicate the necessity of the clean technologies development for pollution abatement and energy. In the last decade most of those technologies relayed on catalysis & active catalytic material applications. Until now, several studies showed correlation of catalyst morphology with its activity & selectivity in given process, i.e. underlying the effects of the catalyst preparation method, operating conditions, and reagents composition. New nanocomposites of high activity, durability and reasonable costs are sought. Therefore, design of catalysts which can selectively operate in different activation ways (thermal-, photo-activation) without activity drop would be beneficial, enhancing potential application perspectives in new & retrofit industrial installation. Understanding the catalyst surface composition, chemical, electronic & morphological transformations of an active phase, as well as active sites arrangement and distribution under reaction condition are of the major importance to optimize the catalytic material and thus better control the whole catalytic process. Inspiration for these studies comes from the publications of Colmenares group: J. Cat. 270 (2010) 136-145; ChemSusChem, 8 (2015) 1676–1685.

The goal: The design of multicomponent intelligent nano-catalytic systems showing enhanced activity in processes such as alternative fuel transformation, selective catalysis or emission control. The project aims at investigating how the performance of nanostructured catalytic materials (nanofibers, nanotubes or nanowires) correlates with their surface composition and active sites distribution.

Our approach: Catalytic materials will be prepared using different techniques, including co-precipitation, impregnation, and sonication methods. Several techniques will be applied for physico-chemical characterization, e.g. X-ray photoelectron spectroscopy, X-ray diffraction, high resolution transmission electron microscopy. Additionally, infrared or ultraviolet–visible spectroscopy can be applied to describe precisely the nature of surface species. In order to investigate materials activity and selectivity in given processes the student will conduct research over a range of temperatures and UV-Vis activation using standard and homemade catalysts, and applying conventional flow/batch (photo)-reactors under atmospheric pressure using well defined gas mixtures and mass spectrometer and/or gas chromatograph as online gas analyser. The Ranido (catalyst manufacturer; Czech Republic) is willing to collaborate on this project.

Current status: In natural recognition mechanisms, complicated biomolecular assemblies are involved. Although this recognition (exploited in biosensors) is mostly specific, the biomolecules suffer from low stability under harsh working conditions. Therefore, artificial recognition systems capable of mimicking recognition functions of corresponding biomolecules are synthesized. Molecularly imprinted polymers (MIPs) are among them. For MIP preparation, first, pre-polymerization complex of dedicated functional monomers and an analyte, initially used as the template, is formed in solution. Next, this complex is polymerized while encapsulating template molecules inside the resulting MIP. Subsequent extraction of the template vacates molecular cavities complementary in their size and shape to the template molecules. That way, a MIP ready for selective recognition exploiting well-defined molecular mechanisms with different types of analyte binding is fabricated. Inspirations for this PhD topic come from the publications co-authored by W. Kutner and F. D'Souza: Biosens. Bioelectron., 2013, 41, 634–641; Biosens. Bioelectron., 2015, 74, 960–966.

The goal: Devising and fabricating MIPs to serve as recognition units of chemical sensors for selective determination of chosen food toxins.

Our approach: We will focus on chemosensing of food toxin analytes incl. representative antibiotics, steroids, heteroaromatic amines, and nitrosamines. Each analyte will require preparing different functional monomers. However, all monomers will share the same electrochemically very conveniently polymerizing thiophenne moiety. Therefore, the student shall electropolymerize a pre-polymerization complex to result in a thin MIP film on a conducting transducer for transduction of a chemical recognition signal into that electric analytically useful. The research will involve: (i) designing, synthesizing, and characterizing new dedicated redox functional and cross-linking monomers capable of electropolymerization, (ii) preparing and characterizing thin MIP films for sensing applications, and (iii) fabricating and testing the chemosensors, featuring MIP recognition units, under flow analytical conditions. The Affinisep (formerly Polyintell; France) and MicruX Technologies (Spain) SMEs will be attracted to commercialize products of the research proposed herein.

Current status: Molecularly imprinted polymers (MIPs) can be used not only for separation and determination of selected compounds in complex matrices, but they can be also applied as selective catalysts. Such materials potentially combine the efficiency of enzymes with high stability and durability. MIPs capable of selective catalysis of variety of reactions, ranging from ozonolysis of nitrophenol to hydrolysis of esters were developed. However, application of MIPs in catalysis is still much less studied than their other applications. Especially, interesting is the combination of imprinting with semiconducting and metallic nanoparticles. This approach allows for the combination of photocatalytic or electrocatalytic processes on nanoparticles with selectivity of the catalytic process assured by MIP layer. Such hybrid materials might be used as highly selective catalysts and photocatalysts of various reactions. Moreover, they can also be used as highly selective and sensitive recognition units in chemosensors, due to signal amplification offered by electrocatalytic and photocatalytic MIP hybrid films. Inspirations for this PhD topic come from the publications co-authored by K. Noworyta, W. Kutner and F. D'Souza: Anal. Chem. 84 (2012) 2154; Biosens. Bioelectron., 2015, 74, 526.

The goal: To synthesize ZnO and TiO2 in the form of thin films or nanoparticles, either directly imprinted with selected analytes, or combined with MIP polymers. To characterize the properties and morphology of designed films and, finally, test their applications as photo- and electrocatalysts.

Our approach: Experiments will consist of electrochemical synthesis of metal oxides (ZnO, TiO2, etc.) molecularly imprinted with selected compounds in the form of thin films or nanoparticles. Material structure will be characterized by X-ray diffraction, as well as by FTIR and Raman spectroscopy. Morphology of the films will be studied by SEM or AFM microscopy. Furthermore, photo- and electrochemical properties of synthesized materials will be studied. These latter will finally be tested as electrocatalysts and photocatalysts for the synthesis and enhanced determination of selected compounds. Practical applications of materials devised for catalysis and sensor development will be studied in collaboration with commercial companies: Affinisep (formerly Polyintell; France) and Micrux (Spain).

The goal: To study the mechanism of disruption of model bacterial cell membranes composed of phospholipid bilayers, by AMPs and the role of cholesterol in protecting a mammalian-like membrane from the AMP attack.

Our approach: The project aims at investigating a promising class of therapeutics capable of destroying multidrug-resistant bacteria. The recruited PhD student will study this disruption mechanism by imaging with atomic force microscopy (AFM), scanning tunneling microscopy (STM), and polarization-modulation infrared reflection-adsorption spectroscopy (PM-IRRAS). (S)he will deposit supported planar phospholipid bilayers (SPLBs) on surface of an atomically flat substrate, e.g. mica or Au(111), both in the absence or presence of AMPs. Next, the student will image the resulting bilayer by AFM and STM under electrochemical conditions. Subsequently, (s)he will conduct the PM-IRRAS study in order to investigate the effect of AMPs on conformation of phospholipid molecules in the bilayers.

Current status: Several recent studies proposed determining levels of the gamma aminobutyric acid (GABA), melatonin & oxytocine nonapeptide biocompounds in body fluids for early autism spectrum disorder (ASD) diagnoses in children. That way, these biocompounds serve as the ASD biomarkers. Melatonin is an endogenous neurohormone predominantly produced in the pineal gland. It is synthesized from L-tryptophan through several metabolic intermediates, most notably serotonin. Physiological levels of melatonin and its derivates are commonly below average in the ASD patients and correlate well with autistic behaviour. Very similarly, recent reports suggested that social impairments found in these patients are associated with changes in the GABA and oxytocin levels in body fluids. In addition to these biomolecular compounds, the recent research confirms the presence of some microorganisms, such as Clostridium bolteae, in stool samples of autism patients. Therefore, detection of these microorganisms will help in early diagnosis of autism. The task of imprinting of whole bacteria is challenging. Therefore, first, we will use model bacteria for developing a procedure of this imprinting. Inspiration for this PhD topic comes from the publications of P. S. Sharma group (Analytica Chimica Acta, 844 (2014) 61-69), and M.Etienne group (Electrochemically assisted bacteria encapsulation in thin hybrid sol–gel films, Journal of Materials Chemistry B, 1 (2013) 1052-1059).

The goal: The long-term perspective is to devise and fabricate robust, efficient, analytically validated molecularly imprinted polymer (MIP) devices as well as to develop procedures for selective quantification of biomarkers in body fluids for early autism diagnosis.

Our approach: To develop chemosensors for above-mentioned biomarkers, the well know technique of molecular imprinting will be applied. The resulting imprinted polymers, in a form of recognition units, will be integrated with different transducers for chemosensor preparation. We will explore several new transducers including surface plasmon resonance (SPR) chips & chemFETs. In the SPR transduction, adsorption or interaction of an analyte with the MIP deposited on the gold chip surface will change the refractive index. In chemFETs, the transduction mechanism will involve chemical modulation of the work function of the gate MIP material by the analyte.

Current status: Secondary organic aerosols (SOA) are air-suspended liquid or solid particles having aerodynamic diameters of less than 10 micrometers and a complex chemical composition. These systems have been the subject of intense multidisciplinary research for the last two decades, as aerosol nanoparticles affect human health, the quality of life and the Earth’s climate. Despite great scientific efforts, our understanding of nanoparticles formation and growth in ambient air, as well as of their processing, is far from thorough elucidation. Volatile plant metabolites belonging to the terpenoid family, including isoprene (C5H8), its oxygenates, monoterpenes (C10H16), and oxygenated aromatics, play a key role in such processes. Owing to unsaturated bonds, these species serve as SOA precursors, being involved in the chain of numerous reactions with atmospheric oxidants, including hydroxy radicals, sulphate radicals and ozone. Although a number of these reactions are not recognized, their unknown products, incl. organosulphates, organonitrates, and nitroxyorganosulphates, add to the aerosol mass and enhance the hydrophilic properties of atmospheric aerosol nanoparticles. Inspiration for this PhD topic comes from the publication co-authored by R. Szmigielski and I. Grgic in Chemical Reviews, 115(10), 3919, (2015) and from the publication of I. Grgic group in Environmental Science & Technology, 49(15), 9150. (2015).

The goal: To recognize the aqueous-phase reactions of selected plant volatiles at the molecular level through off-line and on-line mass spectrometry techniques and kinetic analysis.

Our approach: Experiments envisage application of atmospheric ionization mass spectrometry as a key tool to monitor the reaction course between a selected plant volatile and the atmospheric oxidant, and to compare these results with the analysis of ambient SOA samples collected at various sites. The unknown SOA components that appear at considerable concentrations in the LC/MS traces of aqueous-phase simulation experiments and ambient SOA samples will be characterized using a detailed interpretation of mass spectra, organic synthesis of reference material, kinetic analysis and DFT-based calculations. Obtained data should be of value for the modelling community, helping to improve their air quality models and the models of pollution dissemination in the lower troposphere. The data may also be used by agencies dealing with air monitoring, and in particular - monitoring of air-impacted by non-negligible biomass burning episodes.

13

Towards mechanisms of nanoparticle aerosol formation from selected plant volatiles in the atmosphere: field and laboratory studies

Current status: Atmospheric aerosols were subject to intense multidisciplinary research for the last two decades, but our understanding of the formation, growth, and processing of nanoparticles in ambient air is still in its infancy. Volatile plant metabolites belonging to the terpenoid family play a key role in such processes. These compounds include isoprene (C5H8), its oxygenates, and monoterpenes (C10H16). The presence of double bonds makes them the efficient precursors of aerosol nanoparticles, via a chain of reactions with atmospheric oxidants, including hydroxy radicals, sulphate radicals, and ozone. Although a number of these reactions is not recognized, their unknown products, incl. organosulphates and nitroxyorganosulphates, add to the hydrophilic properties of atmospheric aerosol. Inspiration for these studies comes from the publications co-authored by R. Szmigielski and J. Surrat in Journal of Mass Spectrometry 46 (4), 425, (2011) and Chemical Reviews, 115(10), 3919, (2015).

The goal: To characterize, at the molecular level, the composition and formation mechanisms for the polar organic fraction of ambient aerosols, through field measurements and laboratory simulation experiments.

Our approach: Experiments will focus on the collection of ambient aerosol samples from several sites, the preparation of aerosol extracts, and the respective LC/MS analyses, using atmospheric pressure ionization mass spectrometry. The unknown aerosol components, appearing at considerable concentrations in the LC/MS, will be identified using smog chamber photoxidation and aqueous-phase experiments, organic synthesis of reference material, and DFT-based calculations. Obtained data may be applied to air quality models and models of pollution dissemination in the lower troposphere. The data might be of value to agencies dealing with air quality monitoring.

14

Investigation of lateral distribution of components in biological membranes

Current status: Biological membranes are multicomponent two dimensional fluids. The phospholipids form a bilayer where many different components such as proteins or hydrocarbons are embedded. The behaviour of proteins in biological membranes is still not sufficiently understood. Biological functions of proteins may be modified by their local concentration. The shape of the membrane may depend on the local concentration of components but also the concentration of components may be influenced by the membrane curvature. Inspiration for these studies comes from the publication co-authored by W. Gozdz and A. Iglic in PLoS ONE 8(9) , e73941, (2013) and from publication of W. Gozdz group in J. Chem. Phys., 137(1), 015101, (2012).

The goal: To better understand the physics of multicomponent biological membranes, and to elucidate, how the distribution of different kinds of components influences membrane properties and biological functions, related to differences in the local concentration of components. To describe (experimentally and theoretically) the interaction of biological membranes with nanoparticles and nanostructured surfaces, with the possible application in biomedicine.

Our approach: We will construct and investigate free energy functionals where the geometry of the biological membrane will be taken into account. Such approach combines knowledge from: physics (statistical mechanics), mathematics (differential geometry), biology (lipid membranes & biological cells), material science (fabrication of nanostructures), and computer science (numerical minimization, low level programming).We plan the collaboration with a Slovenian company Sensum d.o.o. (www.hellotrade.com) on the automatic determination of blood cell shapes for diagnostic purposes.

15

Effects of confinement on self-assembly in systems with competing interactions

Current status: Competing interactions are present in soft matter and biological systems, as well as in thin magnetic layers with dipolar interactions, etc. For example, electrostatic repulsion between particles competes with solvent-mediated attraction in soft- and living matter, and ferromagnetic and dipolar interactions compete in thin magnetic layers. Such interactions can lead to self-assembly into various ordered structures on different length scales. The fundamental relation between structural inhomogeneities and mechanical, and thermodynamic properties is not fully understood yet. The type and degree of order, and structural defects in different conditions are still to be determined. In particular, the effect of various system boundaries on the self-assembly remains an open question. These questions are important for potential technological applications of spontaneously ordering systems. Inspiration for this PhD topic comes from the publication of W. Gozdz group in Soft Matter, 9(27) , 6301-6308, (2013) and E. G. Noya group: Soft Matter 10, 8464-8474, (2014).

The goal: To understand the process of pattern formation on a surface, interface or on a membrane in systems with competing interactions. In particular, ordering or disorder induced by various types of system boundaries will be investigated.

Our approach: the PhD student will perform theoretical, numerical, and simulation studies in collaboration with the Rocasalano Institute (CSIC) in Madrid. (S)he will participate in developing the software for graphics processing units (GPUs) commercialised by a small company Sistemas Inormáticos Europeos S.A:U (clustersie.com).

16

Effects of confinement on ionic liquids

Alina Ciach

Enrique LombaThe Institute of Physical Chemistry "Rocasolano", Spain

Current status: Ionic liquids have properties determined by long-range Coulomb interactions, and by the short-range specific potential. Room temperature ionic liquids in porous electrodes are potentially important to innovative electrochemistry. In particular, they are promising for the development of supercapacitors. Transport of ions under confinement has relevance for ionic devices in domains like biophysics, biosensors, on-a-chip laboratories or artificial cells. Thermodynamic, structural, & dynamic properties of ionic liquids/ionic-liquid mixtures near charged surfaces & in porous media are not sufficiently understood. In particular, to date there is no theory able to describe correctly the phase behaviour of confined ionic liquids. Difficulties in theoretical modelling are due to special inhomogeneities & long-range correlations. Inspiration for this PhD topic comes from the papers of E. Lomba group in J. Phys.: Condens. Matter 27 (2015) 194127, and A. Ciach group in Soft Matter, 8, 3567 (2012).

Our approach: The PhD student will perform theoretical, numerical & simulation studies in collaboration with the ROCASOLANO Institute in Madrid. (S)he will participate in developing software for graphics processing units commercialised by a company Sistemas Inormáticos Europeos S.A:U (clustersie.com).

17

Electron spectroscopy of novel nanocarbon systems for applications in medicine

Beata Lesiak-Orłowska

L. KoverInstitute for Nuclear Research of the Hungarian Academy of Sciences, Hungary

Current status: Carbon nanomaterials (carbon nanotubes, graphene oxide, reduced graphene oxide) and their composites with polymers, metals, and metal oxides have recently gained interest in medicine due to their chemical, structural, thermal, mechanical, electro-optical, and photocatalytic properties, and the possibility of modifying these properties. Such carbon nanomaterials of large surface with numerous functional oxygen groups provide possibilities for the attachment of different molecules & nanoparticles, with possible applications for delivery sensors and drugs of designed biocompatibility, targeting at certain electro-optical, photocatalytic, and thermal properties. The description of chemical, structural, electro-optical, photocatalytic, and thermal properties of such drugs is important for revealing their interaction with biological cells and the mechanisms of therapy. Inspiration for these studies comes from the publication co-authored by B. Lesiak and L. Kover in Int. J. Hydrogen Energy, in press (2015) and from the paper of B. Lesiak group in J. Electron Spectroscopy and Related Phenomena 195, 145, (2014).

The goal: To describe the physico-chemical properties of the prepared specimen and to test their biological properties (toxicity), and their potential applications as sensors and drugs for the PDT cancer therapy.

Current status: The techniques of droplet microfluidics have been rapidly developing since 2001. After almost 15 years of research it is possible to execute chemical & biochemical reactions and incubation of microorganisms in nanolitre reactors. There are two major directions of use of these techniques in analytical chemistry and medical diagnostics. The first uses the ability to split liquid samples into thousands or millions of identical micro-droplets and to i) run digital assays that provide absolute quantitation of DNA or immuno-protein targets, and ii) sort large libraries of random mutations either of DNA (e.g. coding enzymes), or plasmids in living bacterial cells. The second direction uses much smaller number of droplets, each prepared with a different chemical composition to execute either a number of different assays, or dilution assays, such as the most commonly used i) quantitation of bacterial load in physiological samples, and ii) antibiotic susceptibility testing. The techniques of droplet microfluidics, however, are still not widely used. The spread of this technology is hampered by the requirement of sophisticated microfluidic instrumentation. Inspiration for this PhD topic comes from the paper of P.Garstecki group in LAB ON A CHIP, 13, 20, 4096-4102 (2013) and R. Zengerle group: ANALYST, 139, 11, 2788-2798 (2014).

The goal: The aim of the PhD project is to develop droplet microfluidic chips that could be operated with the simplest and most common laboratory equipment, i.e. with an automatic pipette. The student will develop systems for i) generation of libraries of identical droplets, ii) generation of libraries of double droplets, and iii) execution of an antibiotic susceptibility test.

Our approach: Expertise of the Garstecki research group and of the Zengerle laboratory will be used for the execution of basic operations on droplets, and initial work on execution of a dilution assay on a chip operated with a pipette, to develop microfluidic systems directly interfaced with an automatic pipette. We will promote short internships of the student in the high-tech startup companies (Scope Fluidics and/or Curiosity Diagnostics at the IPC, and BioFluidix in Freiburg). These activities will facilitate potential transfer of the results to industry.

Current status: Digital assays provide a revolutionary new technology for quantitation of target nucleic acids in a sample. With first demonstrations in the 90's & new commercial apparata that use technology of droplet microfluidics - the digital assays are slowly being launched on the market. The spread of these technologies (in spite of the advantages that include absolute quantitation & potential for simplified workflow) is hampered by i) requirement for massively large no. of partitions (droplets), ii) complexity & high price tag on the devices. Garstecki group has proposed new algorithms for digital PCR that greatly reduce the required no. of partitions of the sample & developed new techniques for passive handling of droplets, incl. preparation of dilutions & splitting of droplets into small libraries. The Zengerle group excels in the techniques of centrifugal microfluidic devices that allow complex liquid handling operations to be performed in a single automated workflow. Inspiration for these studies comes from the paper of P. Garstecki group in ANALYTICAL CHEMISTRY, 87, 16, 8203-8209 (2015) and R. Zengerle group in LAB ON A CHIP, 15, 13, 2759-2766 (2015).

The goal: To develop an integrated centrifugal platform that will take advantage of the new algorithms for the design of digital assays.

Our approach: We will use the combination of expertise of the Garstecki group in passive handling of droplets in microfluidic traps and the expertise of the Zengerle group in the development of centrifugal microfluidic systems to iteratively design & test centrifugal systems that will i) accept the sample & reagents for amplification of the target nucleic acids, ii) prepare the dilutions of the sample, iii) split these dilutions into small libraries of droplets, iv) amplify the target DNA strains in-situ and v) measure the signals from individual droplets. The PhD candidate will also have the opportunity to perform internships in the start-up companies associated with the two firms, in particular: Curiosity Diagnostics (IPC) that develops a system for rapid isolation and amplification of nucleic acids in a traditional, qualitative assay format, and at BioFluidix and/or Cytena, instrumentation companies and spin-offs from the Laboratory for MEMS applications.

20

Mobility of microdroplets - seeking detection strategies that do not require optical labelling

Current status: Progress in microfluidics allows for generation & manipulation of microdroplets comprising liquid samples for chemical & biochemical reactions. These techniques are increasingly used in analytical & diagnostic applications, yet almost all rely on optically-labelled chemicals. Otherwise, selectively attaching a label to a specific chemical in a complex sample like blood certainly is cumbersome. Despite all the benefits to perform a diagnosis on a micro- or nanolitre sample, the current labelling problem hampers the broad use of this technique. Fluid mechanics offers a solution in form of a question how fast droplets travel through capillaries or microchannels. To date, this question remains unsolved. Inspiration for this PhD topic comes from the paper of P. Garstecki group in LAB ON A CHIP, 11, 21, 3603-3608 (2011) and V. van Steijn group in CR. COMPUTERS & FLUIDS, 86, 28-36 (2013).

The goal: To i) characterize experimentally via automated screens mobility of droplets as a function of viscosities of liquids, interfacial tension, wetting angles and cross-section of microchannels, ii) select ranges of parameters that yield high sensitivity of mobility to physical parameters of liquids in a strive to develop a label-free detection strategy of chemical & biochemical processes.

Our approach: We will use the expertise of Garstecki group in building automated droplet microfluidics systems to develop screens of the mobility of the droplets against a large space of combination of the physical parameters. Results of these screens and the expertise of the van Steijn group will be used in modelling & theoretical description of the interfacial and flow phenomena at the microscale to deliver at least empirical scaling relations for the observed changes in mobility of the droplets and hopefully a theoretical model of the physical mechanism behind. Predictions, under what conditions the mobility is most sensitive, will be tested experimentally upon return in the Garstecki lab. This will be used to design a microfluidic system for testing the possibility to detect chemical reactions via observation of changes of mobility of the droplets. Reactions to be tested range from polymerase chain reactions & isothermal amplification of DNA to agglutination reactions.

21

Devolopment of new inorganic-organic hybrid materials for perovskite solar cells

Current status: Within the space of a few years, hybrid organic–inorganic perovskite solar cells have emerged as one of the most exciting material platforms in the photovoltaic. The key material for the perovskite solar cell is the organometal halide CH3NH3MX3 (M = Pb or Sn, X = Cl, Br or I), stabilized mostly as cubic perovskite structures at ambient temperature. Inspiration for these studies comes from the publication co-authored by M. Graetzel and J. Lewiński in J. Mater. Chem. A, 2015, DOI: 10.1039/c5ta04904k and from publication of M. Graetzel group in Nature 2013, 499, 316.

Our approach: Experiments will focus on the syntheses of organohalide perovskites and utilization of ZnO nanocrystals (NCs) with perovskite substrates for the synthesis of metal oxide doped perovskite composites. Attention will be paid to development of mechanochemical perovskites synthesis procedures, as these avoid solvent usage and allow for shortening the reaction times while increasing the product purity. The fabrication of solution-processable solid-state devices will be developed in a close cooperation with the Prof. Graetzel group.

Daniel Lee, Gael De PaepeInstitute for Nanoscience and Cryogenics, France

Current status: Colloidal semiconductor nanocrystals (NCs) are the subject of intense research due to their electronic and physicochemical properties exploited for applications such as catalysis, electronics, photovoltaics, and biomedicine. While scientific research on these nanomaterials was initially mainly oriented toward the physical properties of the inorganic core, interest in the organic ligand shell has shown a steady increase over the last 5 years. Very recently, our group has developed a new general self-supporting organometallic approach to ZnO NCs based on RZn(X)-type precursors (where X = monoanionic monodentate or multidentate organic ligand). Inspiration for these studies comes from the publication co-authored by D.Lee and G.De Paëpe in J. Am. Chem. Soc. 2014, 136, 13781 and from publication of J.Lewiński group in Chem. Eur. J., 2015, 21, 5488.

The goal: The aim of the research proposal covers synthesis and particularly comprehensive spectroscopic characterization of a broad range of ligand-coated ZnO NCs and related semiconductor NCs, i.e. ZnO, ZnS and Zn3P2.

Our approach: The resulting state-of-the-art semiconductor NCs will be characterized with spectroscopic techniques including UV-Vis, infrared, Raman electron spin resonance, steady-state and time-resolved fluorescence, as well as powder X-ray diffraction and transmission electron microscopy. Attention will be paid to the development of modern NMR spectroscopic techniques to characterize the surface NCs and determine the chemical state of coating ligands, as well as observe dynamic surface processes; the techniques to be used include NOESY, Pulsed Gradient Spin-Echo NMR, diffusion-filtered NMR, and, most importantly, Dynamic Nuclear Polarization enhanced solid-state NMR (an emerging hyperpolarization technique currently under development in the collaborators’ group), which will enable a comprehensive insight into the dynamic surface chemistry of the investigated semiconducting NCs.

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 711859.